Investigation of Conditions Giving Minimal Scrambling in the Synthesis of trans-Porphyrins from Dipyrromethanes and Aldehydes

Abstract

A diverse range of reaction conditions for the MacDonald-type 2 + 2 condensation of a 5-substituted dipyrromethane and an aldehyde has been studied with the goal of eliminating acid-catalyzed polypyrrolic rearrangement reactions in the synthesis of trans-porphyrins. A rapid screening method based on laser desorption mass spectrometry has enabled the degree of rearrangement to be examined as a function of the acid catalyst, reagent concentration, reagent stoichiometry, solvent, salts, and temperature. For condensations involving 5-mesityldipyrromethane, we identified reaction at 10 mM concentration in CH(2)Cl(2) with 17.8 mM TFA as optimal conditions for suppression of the rearrangement reaction. A synthetic procedure based on these conditions allowed the expedient synthesis of multigram batches of eight trans-porphyrins in 48-14% yield from 5-mesityldipyrromethane, with minimal chromatography. The same conditions were also effective for the synthesis of two trans-porphyrins derived from 5-(2,6-dichlorophenyl)dipyrromethane. Application of the same conditions to condensations involving 5-phenyldipyrromethane showed extensive rearrangement. Examination of a wide range of conditions showed that slow reactions are associated with less rearrangement. Two sets of conditions were identified that gave little or no scrambling: (1) condensation at 10 mM in MeCN at 0 degrees C with BF(3).Et(2)O catalysis in the presence of NH(4)Cl followed by DDQ oxidation and (2) condensation at 0.1 M in DMSO at 100 degrees C in the presence of NH(4)Cl (with no added acid catalyst) with air oxidation. Although yields are typically less than 10%, the elimination of the need to perform tedious chromatography improves the methodology available for the preparation of trans-porphyrins, derived from sterically unhindered dipyrromethanes.

Boron-Complexation Strategy for Use with 1-Acyldipyrromethanes

“…The metals include Mg(OAc) 2 ·4H 2 O, Sc(OTf) 3 3 , Yb(OTf) 3 , Tl(OAc), and BiCl 3 . The conditions employed treatment of a methanolic solution of 2a 2 (100 mM) with the metal reagent (50 mM) at room temperature for 1 h. Most of the reagents examined gave multiple components.…”

“…To the flask containing the dipyrromethanemoncarbinol (0.250 mmol assuming quantitative reduction) was added reagent-grade CH 2 Cl 2 (50 mL). The mixture was stirred for 5 min to achieve dissolution, and then Yb (OTf) 3 (0.010 g, 0.016 mmol, 0.32 mM) was added. The reaction was monitored by absorption spectroscopy [by injecting a 50 μL reaction aliquot into a solution of DDQ (300 μL, 0.01 M in toluene); then 50 μL of the resulting oxidized mixture was dissolved in CH 2 Cl 2 /EtOH (3:1, 3 mL), and the absorption spectrum was recorded].…”

Stirring the porphyrin alphabet soup—functionalization reactions for porphyrins

“…Acid-catalyzed scrambling in 100 the final step has been an ongoing problem. 13 For selected residues this has been overcome by newer developments, esp. the MgBr 2 /DBU cyclization method.…”

Anthracenylporphyrins

“…Subsequent oxidation with 2,3-dichloro-5,6-dicyanoquinone (DDQ) yields the corresponding porphyrin. This has been proven to be an effective method for A 2 B 2 -type porphyrins in previous studies [16], and thus was applied to the synthesis of A 2 B 2 -type anthracenylporphyrins. The design of the substitution pattern is only limited by the synthesis of the pyrrole derivatives and by the pos-sibility of scrambling [17].…”